Rat liver microsomes convert propranolol to three major metabolites; 5-hydroxypropranolol (50HOr), 4-hydroxypropranolol (40HPr) and desisopropyl-propranolol (Desiprpr). In the presence of both hepatic soluble enzymes and reduced glutahione, the formation of 5-hydroxypropranol was markedly diminished with concommitant increase of glutathione conjugate. More glutathione conjugate was formed with liver microsomes isolated from pretreated with BNF than with those from phenobarbital treated or untreated rats. Accordingly, the covalent binding of active intermediate from propranolol metabolism to a macromolecules of rat liver microsomes was highest with liver microsomes isolated from BNF treated rats.